Perception of alcohol intoxication shows acute tolerance while executive functions remain impaired.

Several psychological constructs (e.g., subjective perception of intoxication, visuomotor speed) display acute tolerance to alcohol, that is, show improvement at declining blood alcohol concentrations (BACs) relative to equivalent rising BACs. However, methodological challenges emerge when attempting to make such comparisons across limbs of the BAC curve, which have proven a barrier to advancing research on acute tolerance. To date, no studies have made multiple comparisons across the entire BAC trajectory. This study employs experimental procedures that overcome some of these difficulties, offering a clearer picture of recovery of impairment for subjective perception of intoxication and cognitive performance and the relationship between them. Twenty participants were assessed at multiple time points over 2 days. Continuous subjective perception of intoxication ratings and cognitive data derived from a computerized measure were paired with a novel analytic paradigm, which allowed comparisons at identified BACs. Results showed acute tolerance for individuals' subjective perception of intoxication and for performance on cognitive tasks measuring visuomotor speed and learning efficiency (recovery from impairment). In contrast, performance on measures of executive function and short-term memory showed no significant difference between limbs at exact concentrations (no recovery from impairment). Therefore, despite participants feeling less intoxicated over time, many cognitive functions remained impaired. The implication for these findings in terms of drunken driving behavior are substantial, suggesting that people may be likely to drive once they subjectively perceive that they have recovered from the acute intoxicating effects of alcohol, despite the persistence of “higher order” cognitive impairments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dose effects of triazolam and scopolamine on metamemory.

The present study compared the acute dose effects of the benzodiazepine triazolam and the anticholinergic scopolamine on metamemory (knowledge and awareness of one’s own memory) in a two-phase paradigm designed to assess effects on both monitoring and control components of metamemory in both semantic (general knowledge) and episodic memory (cued-recall) tasks. Placebo and 2 doses each of triazolam (0.125, 0.25 mg/70 kg, oral) and scopolamine (0.25, 0.50 mg/70 kg, subcutaneous) were administered to 80 healthy volunteers (16 per group) in a double-blind, double-dummy, independent groups design. Both triazolam and scopolamine impaired episodic memory (quantity and accuracy) but not semantic memory. Results suggested that both drugs impaired monitoring as reflected in absolute accuracy measures (impaired calibration in the direction of overconfidence) and control sensitivity (the relationship between confidence and behavior). Overall, the results did not provide evidence for differences between triazolam and scopolamine in memory or metamemory. In addition to the clinical relevance of the observed effects, this study adds to the accumulating body of cognitive psychopharmacological research illustrating the usefulness of drug-induced amnesia as a vehicle to explore memory and metamemory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lorazepam and scopolamine: A single-dose comparison of effects on human memory and attentional processes.

This placebo-controlled, double-blind, double-dummy, independent groups study directly compared effects of the benzodiazepine, lorazepam (2.0 mg/70 kg orally administered), and the anticholinergic scopolamine (0.6 mg/70 kg subcutaneously administered) on memory and attentional measures hypothesized to differentiate the drugs. At the studied doses, lorazepam and scopolamine produced similar decrements in psychomotor performance, free recall, and overall sensitivity in distinguishing between studied and nonstudied items on a recognition memory test. However, the drugs differed with respect to effects on working memory, response bias, metacognition, subjective awareness, and selective attention. In addition to providing information about the cognitive psychopharmacological profiles of drugs with distinct neurochemical and pharmacological mechanisms of action, this study also informs the understanding of memory and attentional processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clubgoers and their trendy cocktails: Implications of mixing caffeine into alcohol on information processing and subjective reports of intoxication.

Alcoholic drink preferences in college students have made an interesting shift recently, with trends in consumption leaning toward caffeinated alcohol in various forms (e.g., Red Bull and vodka or caffeinated beers such as Anheuser-Busch's B-to-the-E). Despite the dramatic rise in popularity of these beverages, little research has examined the combined effects of alcohol and caffeine, which is problematic for adequately informing the public about the risk or lack thereof of these drinks. The purpose of this study was to directly investigate the acute effects of alcohol and caffeine, alone and in combination, on well-validated measures of cognitive performance and subjective intoxication in social drinkers. Participants (N = 12) performed a psychological refractory period task that measured dual-task interference as the prolonged reaction time to complete the 2nd of 2 tasks performed in close temporal sequence. Performance was tested under 2 active doses and 1 placebo dose of caffeine (0.0 mg/kg, 2.0 mg/kg, and 4.0 mg/kg) in combination with 1 active dose and 1 placebo dose of alcohol (0.0 g/kg and 0.65 g/kg). As expected, alcohol impaired task performance by increasing dual-task interference and increasing errors. The coadministration of caffeine counteracted the effects of alcohol on interference but had no effect on the degree to which alcohol increased errors. Subjective measures of intoxication showed that coadministration of caffeine with alcohol reduced participants' perceptions of alcohol intoxication compared with administration of alcohol alone. The results highlight the complexity of drug interactions between alcohol and caffeine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute behavioral effects of triazolam and caffeine, alone and in combination, in humans.

The acute behavioral effects of triazolam (0, 0.375, and 0.75 mg/70 kg) and caffeine (0, 250, and 500 mg/70 kg), alone and in combination, were assessed in 9 male volunteers. Ss received all possible dose combinations according to a Latin square design. Triazolam administered alone dose dependently disrupted learning and performance on the Repeated Acquisition and Performance procedure and the Digit Symbol Substitution Test and increased S ratings of sedation. Caffeine administered alone did not significantly affect learning or performance measures, but it did dose dependently increase S ratings of drug strength. Caffeine significantly attenuated triazolam-induced decrements in learning and performance. Consistent with effects on learning and performance, caffeine offset triazolam-induced increases in S ratings of sedation. Combining caffeine and triazolam did not significantly alter increases in S ratings of drug strength observed with caffeine alone. These effects are qualitatively similar to those observed with other benzodiazepines (e.g., lorazepam) and document a high degree of consistency in the behavioral pharmacology of benzodiazepine-caffeine combinations in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of triazolam and ethanol on proactive interference: evidence for an impairment in retrieval inhibition

The effects of two memory-impairing drugs, ethanol and triazolam, on proactive interference (PI) in memory were studied. Following ingestion of either one of these drugs or a placebo, subjects studied an A-B list (e.g., BEE-WASP) of paired associates, followed by an A-C list (e.g., BEE-HONEY) on the interference trial, and a D-E list (e.g., KING-QUEEN) followed by an A-C list on the control trial. A PI effect was found in the data, such that subjects produced fewer correct second list targets on the interference trial than on the control trial. Neither ethanol nor triazolam was found to influence the size of the PI effect. However, both drugs were found to increase B intrusions on the test of the A-C list, to impair subjects' ability to produce more than one studied response for each cue word, and to impair the subjective experience of retrieved memory information. These data suggest that ethanol and triazolam impair an inhibitory process that normally operates as one component of intentional retrieval, playing an important role in the suppression of unwanted information during a memory task.     

Acute behavioral effects of estazolam and triazolam in non-drug-abusing volunteers.

The present study compared the acute behavioral, participant-rated and observer-rated effects of estazolam and triazolam in 7 healthy, non–drug-abusing humans. Placebo, estazolam (1, 2, and 4 mg), and triazolam (0.125, 0.25, and 0.50 mg) were administered orally in a double-blind, crossover design. Estazolam and triazolam produced orderly dose- and time-related impairment of learning and performance and produced sedative-like participant-rated and observer-rated effects. The absolute magnitude of estazolam's and triazolam's effects at peak effect was comparable across these measures. Triazolam, but not estazolam, impaired immediate and delayed picture recall. The greater effects of triazolam than of estazolam on immediate and delayed picture recall should be viewed cautiously because subtle differences between these drugs in terms of time-to-peak plasma levels may be a confound. Future research should attempt to more thoroughly establish the time–action function of estazolam and triazolam on tasks like picture recall and recognition and determine if the drugs differ at peak effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impairment of semantic and figural memory by acute ethanol: age-dependent effects

Alcohol drinking is prevalent among young adults in the U.S. Moreover, heavy drinking is acknowledged by a substantial percentage of young adults in both college and military subpopulations, despite the known cognitive demands associated with these endeavors and the cognitive impairments associated with alcohol usage. We assessed the acute effects of ethanol (0.6 g/kg) on the acquisition of both semantic and figural memory in a sample of young adults from 21 to 29 years of age using a repeated-measures, placebo-controlled experimental design. Ethanol significantly impaired memory acquisition in both domains. In addition, the effect of ethanol on three of the four memory measures assessed was dependent on the age of the subjects. Subjects in a young subgroup (21 to 24 years of age) were significantly more impaired in memory measures than those in the subgroup that was 25 to 29 years of age. These results indicate a divergence of the potency of ethanol against memory acquisition across a narrow age range in early adulthood. Whereas these data are preliminary, and should be generalized cautiously, they are also consistent with a growing literature using animal models that indicates that acute ethanol is a more potent antagonist of memory and memory-related hippocampal activity in adolescent animals compared with adults.     

Alcohol and social anxiety in males: Behavioral, cognitive, and physiological effects.

To test the tension reduction hypothesis (TRH) of alcohol consumption, 2 studies were conducted to determine the effects of alcohol on heterosexual social anxiety. In Study 1 a clinical population of 32 socially anxious males drank 0 or .5 ml/kg of pure ethanol and then interacted with a female confederate. Expectancies about alcohol consumption and its effects were manipulated by using both a placebo beverage and instructional sets about the positive or negative effects of alcohol. Physiological, cognitive/self-report, and behavioral measures (e.g., Fear Thermometer and the Multiple Affect Adjective Check List) indicated that alcohol produced a marked impairment in the shy Ss while not appreciably affecting physiological responses. Study 2 employed 36 undergraduate males and 3 dosages of alcohol (0, .33, and .75 ml/kg). Once again alcohol impaired both behavioral performance and self-report ratings. In addition, the high-dosage alcohol group experienced greater sustained cardiac acceleration as a function of the social interaction than did the other 2 groups, suggesting the possibility of an alcohol–stress relationship. Data disconfirm the utility of a global TRH in explaining the psychological and physiological effects of alcohol ingestion. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Resistance to cognitive impairment under alcohol: The role of environmental consequences.

This study showed that cognitive impairment under alcohol is affected by environmental factors. Forty male social drinkers were randomly assigned to 4 groups. Participants practiced a task that measured their rate of information processing. Three groups then performed the task under a moderate dose of alcohol (0.62 g/kg) and received either an immediate informative monetary consequence (Ml); a delayed uninformative monetary consequence (M); or no consequence (N) for maintaining their unimpaired processing rate. A control group (C) performed the task without alcohol or any consequence for performance. The processing rates of Groups M and N were slower (i.e. impaired) under alcohol than those of Group C. In contrast, Group MI displayed no significant reduction in processing rate under alcohol (i.e. no impaired). Resistance to the impairing effects of alcohol on information processing is enhanced by a rewarding consequence that conveys information about the adequacy of performance under the drug. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5–15.0 mg), triazolam (0.0625–0.3750 mg), pentobarbital (25–150 mg), caffeine (100–600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deleterious effects of alcohol intoxication: Diminished cognitive control and its behavioral consequences.

The authors tested the hypothesis that impaired behavioral performance during intoxication results partly from alcohol's deleterious effects on cognitive control. The impact of alcohol on perseverative behavior was examined with an n-back working memory task that included manipulations of task complexity and prepotency of inclinations to respond or withhold responding. Thirty-two social drinkers (16 men) participated in either an alcohol (.075g/100ml) or a no-alcohol condition. Alcohol increased perseveration of prepotent, task-inappropriate response patterns only under cognitively demanding (heavy memory load) conditions. This effect was evident for both commission errors (response persistence despite contingencies altered to require restraint) and omission errors (failure to respond when contingencies were revised to encourage action). Findings suggested that alcohol-induced perseveration arises from impairments in cognitive control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cigarette abstinence impairs memory and metacognition despite administration of 2 mg nicotine gum.

The authors assessed the effects of cigarette abstinence (nonabstinent vs. minimum 8 hours abstinent) and nicotine gum (0 mg vs. 2 mg nicotine) on sustained attention, free recall, and metacognition using a within-subjects design. Moderate smokers (10 women and 22 men) received one training session followed by four test sessions on consecutive days. Nicotine gum improved sustained attention in both abstinent and nonabstinent states, but had no significant effect on predicted or actual recall levels. Cigarette abstinence significantly impaired free recall and reduced the magnitude of participants' predictions of their own performance. In addition, participants were significantly more overconfident about their future memory when abstinent. Thus, nicotine gum can improve smokers' performance in basic aspects of cognition (e.g., sustained attention) but may not alleviate the detrimental effects of cigarette abstinence on higher-level processes such memory and metacognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal volume is associated with memory but not monmemory cognitive performance in patients with mild cognitive impairment

Mild cognitive impairment (MCI) appears to be a transitional stage in the development of Alzheimer's disease (AD). Patients with MCI show impaired memory performance and hippocampal atrophy relative to normal elderly controls. Prior studies indicate that the degree of hippocampal atrophy in MCI patients predicts conversion to AD. In contrast to patients with MCI who have deficits primarily in memory, AD patients have clinically evident impairments in both memory and nonmemory cognitive domains. One explanation for the observation that a smaller hippocampal volume predicts conversion to AD might be that hippocampal atrophy is associated with early impairment in nonmemory cognitive areas as well as memory. A link between hippocampal volume and nonmemory function could occur if hippocampal atrophy was correlated with AD pathology in other brain regions. We therefore sought to determine the relationship of hippocampal volume with performance on memory and nonmemory tasks in patients with MCI. Although we found a significant correlation between hippocampal volume and memory performance, we did not find a significant correlation between hippocampal volume and nonmemory performance. We conclude that the relationship between hippocampal volume and risk of AD is likely tied to reduced memory performance and not associated with impairment in nonmemory cognitive domains.     

Specific- and Partial-Source Memory: Effects of Aging.

Normal aging can be associated with impairments in source memory (recollecting an event's context). This study examined the effects of aging on specific-source memory (e.g., remembering which of 4 people spoke a word) and partial-source memory (e.g., remembering the gender of the person who spoke the word). When young and older adults were matched in terms of old-new recognition, age-related deficits were observed on both specific- and partial-source recollection. When the groups were matched on partial-source performance, no disproportionate specific-source impairment was seen. The results suggest that aging does not differentially affect specific- versus partial-source memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol tolerance in humans is enhanced by prior caffeine antagonism of alcohol-induced impairment.

The author tested the hypothesis that a history of drug-induced antagonism of alcohol impairment would enhance alcohol tolerance in humans. Groups of participants (N = 21) repeatedly performed a psychomotor task under different drug treatments: 0.65 g/kg alcohol, 4 mg/kg caffeine, or both drugs combined. Tolerance to a 0.65 g/kg alcohol dose challenge was then tested. Results showed that a history of combined alcohol and caffeine administrations increased alcohol tolerance compared with an exposure history to either drug alone. The findings contribute to the understanding of the complexities of polydrug use history and provide a useful model to examine how alcohol tolerance might be affected by a history of coadministration with other drugs (e.g., cocaine and nicotine). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The protective effect of moderate alcohol consumption on ischemic stroke

Experiments were designed to investigate the influence of estrous cycle and gender of the rat on the effects of a gamma-aminobutyric acid type A (GABA(A)) receptor active neurosteroid, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), the benzodiazepine, triazolam, and a GABA(A) receptor antagonistic neurosteroid, delta5-androsten-3beta-ol-17-one sulfate (dehydroepiandrosterone sulfate), on food intake and elevated plus-maze learning behaviors. Allopregnanolone (0.25 mg/kg, s.c.) and triazolam (0.25 mg/kg, i.p.) produced a hyperphagic effect, while dehydroepiandrosterone sulfate (5 mg/kg, s.c.) elicited an anorectic effect. However, allopregnanolone was more potent in diestrous females, whereas triazolam exhibited significantly higher hyperphagic potency in estrus females. The extent of anorexia following dehydroepiandrosterone sulfate was alike in male and female rats. The triazolam- and allopregnanolone-induced hyperphagic effect was blocked by bicuculline (1 mg/kg, i.p.), a selective GABA(A) receptor antagonist. In contrast to triazolam, the hyperphagic effect of allopregnanolone was insensitive to flumazenil (5 mg/kg, i.p.), a benzodiazepine antagonist. Vehicle-treated diestrous rats displayed moderately higher latencies in the elevated plus-maze learning task than estrus or proestrus females. Although allopregnanolone and triazolam elicited equipotent learning deficits in plus-maze learning in male and female rats, the magnitude of impairment-induced by triazolam was significantly higher in diestrous females than proestrus females. Dehydroepiandrosterone sulfate enhanced memory performance only in male rats. Although the use of the elevated plus-maze as a learning paradigm with benzodiazepines and neurosteroids may be sensitive to changes in anxiety, the differential data suggest that neurosteroid-induced effects are at least partly specific to learning behavior. These results confirm the role of estrous cycle and sex of rats in modifying the potency of neurosteroids and benzodiazepines on food consumption and learning and memory processes.     

Cognitive processes in dissociation: An analysis of core theoretical assumptions.

Dissociation is typically defined as the lack of normal integration of thoughts, feelings, and experiences into consciousness and memory. The present article critically evaluates the research literature on cognitive processes in dissociation. The authors' review indicates that dissociation is characterized by subtle deficits in neuropsychological performance (e.g., heightened distractibility). Some of the cognitive phenomena (e.g., weakened cognitive inhibition) associated with dissociation appear to be dependent on the emotional or attentional context. Contrary to a widespread assumption in the clinical literature, dissociation does not appear to be related to avoidant information processing. Rather, it is associated with an enhanced propensity toward pseudo-memories, possibly mediated by heightened levels of interrogative suggestibility, fantasy proneness, and cognitive failures. Evidence for a link between dissociation and either memory fragmentation or early trauma based on objective measures is conspicuously lacking. The authors identify a variety of methodological issues and discrepancies that make it difficult to articulate a comprehensive framework for cognitive mechanisms in dissociation. The authors conclude with a discussion of research domains (e.g., sleep-related experiences, drug-related dissociation) that promise to advance our understanding of cognition and dissociation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Simulated driving performance of adults with ADHD: Comparisons with alcohol intoxication.

Previous research has demonstrated that adults with attention deficit/hyperactivity disorder (ADHD) are more likely to experience driving-related problems, which suggests that they may exhibit poorer driving performance. However, direct experimental evidence of this hypothesis is limited. The current study involved 2 experiments that evaluated driving performance in adults with ADHD in terms of the types of driving decrements typically associated with alcohol intoxication. Experiment 1 compared the simulated driving performance of 15 adults with ADHD to 23 adult control participants, who performed the task both while sober and intoxicated. Results showed that sober adults with ADHD exhibited decrements in driving performance compared to sober controls, and that the profile of impairment for the sober ADHD group did in fact resemble that of intoxicated drivers at the blood alcohol concentration level for legally impaired driving in the United States. Driving impairment of the intoxicated individuals was characterized by greater deviation of lane position, faster and more abrupt steering maneuvers, and increased speed variability. Experiment 2 was a dose-challenge study in which 8 adults with ADHD and 8 controls performed the driving simulation task under 3 doses of alcohol: 0.65g/kg, 0.45g/kg, and 0.0g/kg (placebo). Results showed that driving performance in both groups was impaired in response to alcohol, and that individuals with ADHD exhibited generally poorer driving performance than did controls across all dose conditions. Together the findings provide compelling evidence to suggest that the cognitive and behavioral deficits associated with ADHD might impair driving performance in such a manner as to resemble that of an alcohol intoxicated driver. Moreover, alcohol might impair the performance of drivers with ADHD in an additive fashion that could considerably compromise their driving skill even at blood alcohol concentrations below the legal limit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Triazolam-induced changes in alcoholic thought processes

This study was designed to examine and contrast cognitive effects (explicit memory and access to semantic knowledge) of the benzodiazepine Halcion (triazolam) in ten normal volunteers and ten cognitively un-impaired detoxified alcoholics. The two groups were indistinguishable from one another under placebo conditions on all measures of cognitive functioning. Under Halcion test conditions (0.375 mg p.o.), both groups were about equally impaired in their recall of to-be-remembered information. However, alcoholics, were more likely to recall information that they were not asked to remember (intrusion errors) on all measures of explicit remembering. Alcoholics also generated relatively uncommon (low frequency) responses from semantic memory, rather than common, categorically related associations in response to stimuli such as types of vegetables, flowers, and fruit following the administration of Halcion, but were not different from normal volunteers in the types of responses generated under placebo conditions. These findings suggest that a drug challenge that simulates many of the effects of acute alcohol administration induces alcoholics to think and remember differently (qualitatively) from normal volunteers.